Abstract:AIM:To investigate the neuroprotective effects of soy isoflavones(SI)against glucocorticoid-induced retinal ganglion cells(RGCs)injury in a rat model of acute ocular hypertension(AOH), and to explore the underlying mechanism involving the PI3K/Akt/Caspase-3 signaling pathway.
METHODS:A total of 48 Sprague-Dawley(SD)rats(48 eyes)were randomly assigned to four groups(n=12 per group): a control group(received normal saline), an AOH control group, a low-dose SI intervention group [LSI+AOH, 360 mg/(kg·d)], and a high-dose SI intervention group [HSI+AOH, 540 mg/(kg·d)]. The AOH, LSI+AOH, and HSI+AOH groups received subconjunctival injections of dexamethasone to induce AOH control group. From the 3 wk of modelling, SI was administered via intraperitoneal injection until 4 wk. Intraocular pressure(IOP)was monitored, RGC density was assessed, and the protein expression levels of PI3K/phosphorylated Akt(p-Akt)/Caspase-3, and key inflammatory cytokines were evaluated.
RESULTS:IOP was significantly higher in the AOH control group compared to the control group(P<0.01). Both the LSI+AOH and HSI+AOH groups exhibited a marked reduction in IOP compared to the AOH control group(all P<0.01). RGC density was significantly lower in the AOH control group than in the control group(P<0.01), but was notably increased in the LSI+AOH group and the HSI+AOH group compared with the AOH control group(all P<0.01). Compared with the control group, the AOH control group demonstrated downregulated protein expression of PI3K and p-Akt, alongside upregulated expression of activated Caspase-3(all P<0.05). After intervention, the expression of PI3K and p-Akt was upregulated, while Caspase-3 was downregulated in the LSI+AOH group and the HSI+AOH group(all P<0.01).
CONCLUSION: SI ameliorates glucocorticoid-induced RGCs injury, potentially by activating phosphorylated Akt(p-Akt)and subsequently inhibiting Caspase-3-mediated apoptosis. These neuroprotective effects appear to be dose-dependent.
